Principal Investigators

Expertise - Work on ageing-related diseases is one of the core activities of Prof. Michel Simonneau's group. Over the last 5 years the group has focused on developing state of the art technologies for functional genomics of genes involved in multifactorial psychiatric diseases. This work has led to a series of papers on synaptic dysfunction in animal models of human disease including the European LOAD-GWAS papers on gene associated to LOAD.

Role in AgedBrainSYSBIO - Michel Simonneau is AgedBrainSYSBIO's coordinator and is involved in WPs 1, 2, 3 and 4. The group will be participation in curating data (WP1); focus on providing novel quantitative description of protein-protein interactions of LOAD-GWAS gene products and other key proteins identified from modeling, using novel models from patient-derived neurons and mouse transgenic lines (WP2); manipulate patient-derived iPScs using BAC constructs and rare variants from LOAD-GWAS patients to be analyzed and tested in relevant models (WP3); and finally make the final constructs of intrabodies using an aav strategy (WP4)

Expertise - The Neurodegenerative Brain Diseases group of the VIB Department of Molecular Genetics (VIB-DMG) headed by Prof. Christine van Broeckhoven, University of Antwerp, is a national and internationally recognized excellence center for neurodegenerative brain diseases research. The group has near 30 years of experience in molecular genetics of Alzheimer and related neurodegenerative brain diseases, playing a crucial role in the elucidation of the genetic underpinnings of these diseases, both for the Mendelian and the genetically complex forms. A strong network with clinicians at the national level ensures follow-up of patients, and a large biobank allows translation of genetic findings to ex vivo patient material. The biobank of the VIB-DMG holds biomaterials of an extended research cohort of (amongst others) 1314 Alzheimer patients and 1223 control individuals of Flanders-Belgian origin.

Role in AgedBrainSYSBIO - WP2: Quantification of gene products in patient biomaterials. WP3: collection of skin samples for culture of fibroblast cell lines, which will be used for the generation of iPSC. Identification of genetic variants underlying GWAS signals, that can be studied further in light of the proposal

Relevant publications

Bettens K, et al. (2012) Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk. Mol Neurodegener. 7(1):3.

Expertise - Dr. Jean-Charles Lambert is recognised expert in the field of Alzheimer’s Disease genetics. The team is mainly interests in to characterize the AD genetic components but also to improve our understanding of how these determinants modify the AD pathophysiological process. Since 2006 the team has published more than 68 peer reviewed articles and registered three patents.

Role in AgedBrainSYSBIO - Jean-Charles Lambert will participate to the efforts in WP3 manipulating pathways using human iPSC-derived neurons, mouse and drosophila models.

Expertise – Dr. Yann Herault is an expert in mouse genetics and director of the Mouse Clinic Institute (ICS), an infrastructure of excellence, which provides services for the scientific community. The ICS has a long tradition of collaboration with both academic community and pharmaceutical industries with more than a 1000 of mouse models generated in the last 9 years, and with an international recognition The ICS is equipped with integrated facilities for genetics, cellular and molecular biology, and notably for creation and characterization of genetically engineered mouse models.

Expertise – Prof. James Adjaye hasextensive experience in the derivation and characterization of iPSCs from dermal fibroblast from healthy individuals but also Alzheimer’s disease patients, differentiation of iPSCs into neuronal cells and analysis of aged related transcriptional changes in mouse tissues, human dermal fibroblasts and iPSCs derived from dermal fibroblasts of aged individuals. Since May 2012 Prof Adjaye is the Director of the newly established Institute for Stem Cell Research and Regenerative Medicine (ISRM) at the Heinrich Heine University, Düsseldorf, Germany.

Role in AdedBrainSYSBIO – James Adjaye will lead the efforts in WP3. The tasks include; (1) Genome wide transcriptome comparison of dermal fibroblasts derived from Alzheimer’s patients and aged matched (40yrs and 80 yrs) healthy controls; (2) Derivation and characterization of patient-specific iPSCs to enable further differentiation of human neurons subtypes: principal cortical neurons and inter-neurons and(3) Manipulating neurons from patient-specific iPSCs.

Prigione A et al. (2011). Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in both young and aged donor-derived iPS cells despite chromosomal aberrations.PLoS One.6(11):e27352

Expertise – Prof. Tal Pupko’s main research interests focus on fields of Molecular Evolution and Bioinformatics and notably on studying the evolutionary selective forces shaping genes and genomes and the in-silico predictions of these forces using probabilistic evolutionary models. Tal Pupko has published several papers on alignment methods and alignment reliability (The program Guidance), developed a webserver for predicting functional regions in proteins (Consurf), and a web server to detect positively selected sites (Selecton).

Role in AgedBrainSYSBIO – The group will be in involved in the following tasks in WP1: (1) Establish multiple sequence alignments in high throughput manner; (2) To filter unreliable alignment regions; (3) To construct phylogenetic trees from all these alignments; (4) To search signature of selection (accelerated evolution or positive selection) in the lineage leading to human. From those genes that are relevant to ageing and show patterns of positive selection in the lineage leading to human, candidate will be chosen for detailed characterization.

Expertise – Dr Jean-Christophe Rain is Director Industrial Operation and Technology Development, at HYBRIGENICS Services. He is the company founder and expert in yeast two hybrid technology with 34 peer review publications in this field and 10 patents. During TrioH (FP6 LSHB-CT-2003-503480), HYBRIGENICS conducted a vast interaction mapping in the HIV field. This work lead to many scientific publications but also to the identification, characterization and validation of a new anti-HIV target now used for drug discovery program in the biotech and pharma industry..

Role in AgedBrainSYSBIO – Jean-Christophe Rain is leading WP2 and responsible for the following tasks: (i) Screening of in human and drosophila library using bait protein selected for their relevance in brain ageing. Construction of libraries of specific neurons and interneurons subtypes. (ii) Display of the interacting data through an optimized display software. (iii) Curation relative to interaction data in the knowledge database. (iv) Modelling process relative interaction network and domain-domain interactions and interaction localization.

Expertise – Jaak Vilo has a long-standing expertise in bioinformatics data mining. He was pioneering the gene expression data analysis and database setup at the European Bioinformatics Institute.Prof. Vilo manages a bioinformatics research group BIIT (http://biit.cs.ut.ee ) and is well known expert in the field of gene expression and bioinformatics data mining areas. The ENFIN project (2006-2011) developed systems biology approaches for network reconstruction and simulations, especially in stem cells. This expertise will be brought over to the ageing and related pathologies investigations.

Role in the project - QURETEC will lead WP1 and develop the omics data management and analysis platform. In collaboration with other WP-s like WP3 a consortium data analysis pipeline and database interface will be developed allowing project partners seamlessly interact with these data over the web interfaces.

Expertise – Dr. Harald Kranz has extensive experience in DNA engineering. The scientific service group headed by Dr. Kranz at GENEBRIDGES has provided academic institutes with DNA engineering services for nearly ten years. Services include the generation of tailored constructs for animal or cell culture models by Red/ET recombination.

Role in AgedBrainSYSBIO – GENEBRIDGES is involved in WP2 and WP3 with the following main tasks: In preparation for immunoprecipitation experiments, GENEBRIDGES will modify key genes identified in LOAD-GWAS by adding tap-tags for the derivation of BAC transgenic and knock-in mouse lines. A further objective is the creation of humanized mouse alleles, through the generation of targeting constructs in which mouse exons have been replaced by their human counterparts. Insertion of point mutations into the targeting constructs will allow analysis of the relevance/effect of SNPs in disease-related alleles.

Expertise – reMYND CRO has 10 years of experience as a partner in preclinical research activities to test experimental treatments against AD in animal models. The PI involved in the project Dr. Dick Terwel, holds a PhD in Neuroscience and has a vast background in preclinical AD research. Prior to joining reMYND, he has been working as post-doctoral researcher at the Department of Human Genetics of Leuven University and as Senior Scientist and Lecturer at the Department of Neurology of University Clinics Bonn.

Role in AgedBrainSYSBIO – reMYND is leading WP4 activities. Main tasks include: (i) Testing of intrabodies targeting protein-protein interaction of GWAS products in screens recapitulating noxious properties of pathological protein aggregates involving toxicity and functional read-outs. (ii) Testing of subset of intrabodies in mice involving determination of intrabody distribution and levels of expression in mouse brain and functional changes at the synapse. (iii) In depth investigation of efficacy of intrabodies on pathology, synaptic markers and behaviour in Tau.P30L- and APPLd mice.

Relevant patentsWO 2007/140933 Methods and tools for the screening of factors affecting protein misfolding.WO 2007/090617 Thiadiazole derivatives for the treatment of neuro-degenerative diseasesWO 2008/061781 Thiadiazole derivatives for the treatment of neuro-degenerative diseasesWO 2009/019295 Phenyl- and benzylthiazolypiperazine derivatives for the treatment of neuro-degenerative diseasesWO 2010/142801 Indole amide derivatives and related compounds for use in the treatment of neurodegenerative diseases

Expertise – Dr. Henning Hermjakob is expert in the development and implementation of data standards for network and pathway data. The group has a long experience in encoding and annotating pathways and models. It has maintained reference computing resources for sharing these datasets during many years, including standard formats, annotation schemes and databases and is in charge of worldwide reference data resources in proteomics (PRIDE), interactomics (IntAct), pathways (Reactome) and models (BioModels Database).

Role in AgedBrainSYSBIO – WP1:The group will focus on extracting from public resources existing interaction networks, pathways and models, in a form suitable for the tasks of the other partners. It will also encode the interaction networks, pathways and models generated by the project in standard formats, suitable for sharing with the community through AgedBrainSYSBIO database and public repositories. Dr. Hermjakob will also be strongly involved in dissemination and training activities and lead WP5.

Expertise – Dr. Ioannis Xenarios is the Director of Vital-IT. He has extensive experience in computational methodologies in the area of proteomics, microarray, genetics and dynamical systems modeling.

Role in AgedBrainSYSBIO – WP1:Together Vital-IT and SwissProt will contribute to AgedBrainSYSBIO by providing expertise, tools and methodology for integration of data sets coming different technologies and expertise for the creation of manually curated regulatory networks and in simulating in silico tools the dynamical behaviours of the curated regulatory network. Furthermore, the group will perform large epistasis analysis of LOAD-GWAS data taking advantage of developed algorithm in quantitative phenotypic analysis. Ioannis Xenarios will also be involved in dissemination and training activities in WP5.

Expertise – Dr. Nicolas Le Novère is a leading figure in the field of pathway and model sharing, being a creator of SBML, SBGN and developer of BioPAX. The group created BioModels Database, the world leading database of systems biology models, now part of the EBI Proteomics Services. During its period at the EBI, the research of the group focused on modelling neuronal signalling, using various approaches and granularity. Dr. Le Novère is a partner of SynSys, an FP7 project dedicated to the systems biology of synaptic function.

Role in AgedBrainSYSBIO – WP1 From information existing in public resources and literature, as well as knowledge generated by other partners, the group will reconstruct key pathways involved in neuron ageing and etiology of AD. It will then develop computational models of selected ones, in order to predict perturbations for testing by the other workpackages. The group will advise on encoding and sharing pathways and models generated by the project in standard formats.

Expertise – Dr. Christiane Dascher-Nadel has extensive experience in both academic and industrial R&D research and has been active in the field of EC project management for the past nine years. She is heading a management team within Inserm Transfert’s European and International Affairs department mainly focused on research projects related to stem cells and biotherapy.

Role in AgedBrainSYSBIO - Christiane Dascher-Nadel is leading WP6 – Project Management and Coordination. She will ensure a professional driving of the project, provide the partners with adequate communication tools and implement an appropriate strategy for knowledge management. In WP5 she will coordinate dissemination and communication activities.

Expertise – Esther-Marie is Co-Founder and Head of the MEA Laboratory at Neuroservice. Esther-Marie has managed Neuroservice’s MEA Laboratory since its inception. Over an 11-year experience with this technique, she has developed and validated dozens of pharmacological and screening assays. Working in close collaboration with scientists from many big pharmaceutical and biotech companies, she has gained a unique experience in drug testing on acute slices with MEA. Esther trained in Biochemistry and earned a Master’s Degree in cellular engineering from the University of Nancy, France.

Role in AgedBrainSYSBIO - Neuroservice is involved in the WP4. It will consist in determining synaptic plasticity properties at 3 different hippocampal synapses and cortical synapses of Wild Type (WT) and Transgenic (Tg) mice.

Last update on 2017-07-22

AgedBrainSYSBIO has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No 305299